QTc interval prolongation in children with Ulrich-Turner syndrome

Introduction The Ullrich-Turner-Syndrome (UTS) is the most commonly occurring sex chromosome abnormality in females. Cardiac malformations are well known, but no data exist on specific electrocardiogram (ECG) patterns in children and adolescents. A prolongation of the QT interval on the ECG has been correlated to an increased risk for sudden cardiac death, and medical treatment is warranted in patients with long QT syndrome (LQTS). Moreover, several drugs of common use are contraindicated in LQTS because of their effects on myocardial repolarization.Methods The ECG tracings of 86 UTS patients [mean age (±SD): 11.0±3.6 years; mean height-SD: −2.6±1.0] were analyzed and compared to age-matched control groups of 75 boys (mean age: 11.3±3.5 years; mean height-SD: −1.9±1.0) and 62 girls (mean age: 10.1±3.2 years; mean height-SD: −2.5±0.9) with short stature.Results Eighteen UTS patients (20.9%) had an abnormally prolonged QTc >0.45 s in contrast to only one control subject (0.9%). The QTc interval of UTS patients was significantly prolonged compared to that of the controls (p<0.01) and normal values.Conclusions There is an increased prevalence of a long QT interval among UTS patients. This should be taken into account for the cardiovascular screening of such patients. Patients with UTS have an intrinsically prolonged QT interval and as such may be at higher risk for arrhythmias in the context of a QT-prolonging medication.R. Dalla Pozza and S. Bechtold contributed equally to this publication.     

Defibrillator Implantation in a Child with Long QT Syndrome

We report the placement of an implantable cardiac defibrillator as preventative treatment in a 2-year-old with long QT syndrome.     

Coincidence of Long QT Syndrome and Propionic Acidemia

Propionic acidemia and long QT syndrome (LQTS) are rare disorders. In addition, both conditions are potentially lethal. The patient presented in this article was initially diagnosed with propionic acidemia. Incidentally, she was found to have LQTS on electrocardiogram and verified by stress test and epinephrine challenge. Although the patient was asymptomatic and arrhythmia free, we started her on atenolol. This is the first report of the association between LQTS and propionic acidemia.     

Implantable Cardioverter Defibrillator Therapy in Children with Long QT Syndrome

We report our experience with implantable cardioverter defibrillator (ICD) implantation and follow-up in high-risk patients with congenital long QT syndrome (LQTS). Congenital LQTS is associated with significant risk of malignant ventricular arrhythmias and sudden cardiac death (SCD). ICD implant is recommended for prevention of SCD in this patient population, but there are few published data regarding the efficacy and side effects of such therapy. We report our experience with 12 patients who underwent ICD implant for high-risk LQTS at our center in the past 5 years with respect to implant complications, appropriate and inappropriate therapies, device follow-up, and the impact on lifestyle. During a follow-up of 34.7 ± 16.6 months, appropriate therapies were noted in 5, inappropriate therapies in 4, and no therapies in 3 patients. Clusters of appropriate therapies were seen in 3 patients, 1 of whom subsequently died. Female sex and congenital deafness appear to be associated with a higher risk of appropriate therapies. One patient experienced two complications at implant that were successfully treated. ICD implantation in LQTS patients presenting with SCD or recurrent syncope despite beta-blocker therapy appears to be justified in preventing SCD risk. In asymptomatic siblings of SCD patients, the benefits of ICD implant are not clear from our data.     

Macroscopic T wave alternans in long QT syndrome

A 6 year old girl was admitted with recurrent episodes of loss of consciousness. ECG showed prolonged QT interval and macroscopic T Wave alternans. Identification of this ECG pattern is important since it can lead to potentially lethal arrhythmias.     

Role of vagotony in sinus node dysfunction in children with symptomatic congenital long QT syndrome

The present study examined chronotropic dysfunction and the role of vagotony in congenital long QT syndrome, sinus node function and the effects of parasympathetic blockade. Six patients with congenital long QT syndrome were studied. The four males and two females, aged 1–15 years, had episodes of syncope and malignant ventricular arrhythmias. Congenital long QT syndrome was defined as a corrected QT interval greater than 0.45 s, T wave alternans and the age at diagnosis. The sinus heart rate measured from a 24 h electrocardiograph was abnormally low (< 50 min) in three patients (1, 4 and 5 years old) and did not increase sufficiently with the administration of atropine in five of the six patients with congenital long QT syndrome. From intracardiac electrophysiological studies, the corrected sinus node recovery time was prolonged in three patients and the total sinoatrial conduction time was prolonged in two patients. In most patients who had an abnormally long sinoatrial conduction time and corrected sinus node recovery time, these values returned to normal following atropine administration. In one patient, the corrected sinus node recovery time was prolonged paradoxically by atropine. Sinus node dysfunction in congenital long QT syndrome was affected by vagotony associated with a right sympathetic nerve system abnormality.     

Long QT syndrome manifesting as pulseless epilepsy

A-10-year-old child admitted with repeated seizures due to the long QT syndrome is described. The cardiac origin of the epilepsy was suggested by the fact that during the episode of convulsions his peripheral pulses were not palpable     

Dilated Cardiomyopathy Masquerading as Long QT Syndrome

Atrioventricular block has been described in association with cases of long QT syndrome and mortality is increased in this subgroup. We describe an infant with congenital QT prolongation and atrioventricular block with normal cardiac function, leading to the initial diagnosis of long QT syndrome. She subsequently developed dilated cardiomyopathy requiring cardiac transplantation. We postulate that the presenting electrocardiograph abnormalities were early manifestations of the myocardial disease, preceding the development of myocardial dysfunction by several months. The need for heightened surveillance in cases of QT prolongation with atrioventricular block is amplified by the possibility of an evolving cardiomyopathy.     

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??Long QT syndrome??LQTS?? is the first found genetic ion channel disease. LQTS patients can show various clinical types?? from a lifetime of being asymptomatic to infantile sudden death?? which can cause malignant ventricular arrhythmia?? syncope?? epileptic seizures?? cardiac arrest and sudden cardiac death. The genetics of LQTS pathogenesis is currently considered specific genetic mutations that can lead to abnormal procedure of depolarization and repolarization of cardiac muscle cell. At the molecular level?? the pathogenesis of LQTS is the 15 different susceptible gene mutations of alpha and beta subunit that encoded ion channels. KCNQ1??KCNH2 and SCN5A mutations account for more than 90% of all mutations in patients with LQTS??and the remained 12 mutations account for only less than 10%. Precision medicine for LQTS mainly lies in the application of beta receptor blockers. Currently it’s believed that beta receptor blockers is better in the treatment of LQTS1 than in LQTS2 and LQTS3. Patients with LQT3 have low beta adrenergic receptor density?? and attacks are mainly related to rest and slow heart rate. Sodium channel blockers are more often recommended in clinical treatment??such as mexiletine??fluorine carney??etc.     

Prenatal Diagnosis and Management of Fetal Long QT Syndrome

This report describes a fetus presenting with second-degree atrioventricular block, sinus bradycardia, and transient ventricular tachycardia with ventriculoatrial dissociation. Long QT syndrome (LQTS) was suspected due to the association of heart rhythm disturbances and very short transmitral early deceleration time. This impaired relaxation of the left ventricle was explained by the extreme prolongation of the refractory period caused by the prolonged relaxation time. The infant was treated successfully with beta-blockers and implantation of a pacemaker. The prognosis is poor when LQTS presents utero or during the first week of life. To date, only a few case reports of a fetus with LQTS have been published.     

中国儿童短QT综合征首例报告及家系调查

目的探讨中国儿童短QT综合征的临床特征及遗传学特点。方法对中国医科大学附属第一医院儿科于2006年收治的1例儿童短QT综合征患儿(患儿男,13岁,以晕厥、抽搐1次为主诉入院,既往健康)临床资料进行分析,并对患儿父母两个家系的22名成员进行遗传学调查。结果查体无异常所见。体表心电图示窦性心律,Q-T间期240ms,QTc270ms,Ⅱ、ⅡI、avF、V4-6导联T波高尖;Holter心电图除见上述改变外,还可见房性和室性期前收缩,心脏彩色超声和心脏X线片未见异常;心肌酶谱、肌钙蛋白和血钾、钠、钙等离子检测值均在正常范围。家系调查表明患儿母亲于12年前猝死在家中,之前曾有反复晕厥、抽搐发作史。体表心电图示Q-T间期260～280ms,T波高尖。在多次住院抢救观察期间,心电图显示尖端扭转型室速、心室颤动。除患儿母亲外,其他成员均无晕厥、抽搐及猝死史,患儿父亲心电图Q-T间期380ms,其他健在者也未见Q-T间期缩短。结论短QT综合征可表现为晕厥、抽搐发作,心电图Q-T间期缩短、QTc≤300ms,心脏结构正常,可有家族猝死史。本例符合常染色体显性遗传。     

Cardiac arrhythmias mimicking primary neurological disorders: a difficult diagnostic situation

Cardiac arrhythmias can present with the signs and symptoms of a seizure disorder. This potentially life–threatening underlying cause of non–febrile seizures should be recognized early, since successful specific treatment is possible. The purpose of this retrospective study was to examine common features in such patients. Over a period of 25 years, eight patients were initially treated for up to 5 years at our institution for a seizure disorder until dysrhythmia as the underlying cause of the seizures was disclosed. The main symptom was drop attacks coinciding with physical activity or emotional stress. Convulsions were only rarely observed. In five of the eight patients the underlying disorder was the long–QT–syndrome (Romano–Ward syndrome). In one patient intermittent complete atrioventricular block was found, another patient showed ventricular tachydysrhythmia of unknown etiology and the last patient suffered from hypertrophic cardiomyopathy.     

Clinical and electrophysiological features of Japanese pediatric long QT syndrome patients with KCNQ1 mutations

Background: The purpose of the present paper was to determine the clinical and electrophysiological features of Japanese pediatric long QT syndrome (LQTS) patients with KCNQ1 mutations (LQT1). Methods: KCNQ1 mutations were analyzed in 13 Japanese pediatric patients with prolonged QT interval on electrocardiogram (ECG). These LQT1 patients were reviewed, retrospectively, for the presence of past and family histories of LQTS‐related cardiac events, other complications, and their ECG findings evaluated at rest and during exercise). Results: KCNQ1 mutations were identified in eight patients (61.5%) from six unrelated families. Four missense mutations were identified in seven patients and an insertion/deletion in one. The mutations were located in the transmembrane domain in four patients and the C‐terminal domain in four. Syncope did not occur in patients with the C‐terminal domain mutations up to the age of 6–9 years, but family members of patients with the C‐terminal domain mutations had a history of syncope in their elementary school days. Compared with a non‐LQTS control group, peak heart rate (HR) on exercise and the HR increase during exercise were significantly lower in the LQT1 group (LQT1 vs control, 155 ± 16 beats/min vs 182 ± 13 beats/min, P < 0.01, 66 ± 16 beats/min vs 99 ± 24 beats/min, P < 0.01, respectively). Conclusions: The risk of LQTS‐related cardiac events may not be different in pediatric LQT1 patients with C‐terminal domain mutations than in patients with transmembrane domain mutations. Possible sinus node dysfunction or a poor HR response to sympathetic stimulation has been suggested in pediatric LQT1 patients.     

β-Blocker Therapy Failures in Symptomatic Probands with Genotyped Long-QT Syndrome

-Blocker therapy is one of the principal therapies for congenital long-QT syndrome (LQTS). However, breakthrough cardiac events occur while being treated with -blockers. We sought to determine the frequency of and clinical correlates underlying -blocker therapy failures in genotyped, symptomatic LQTS probands. The medical records were analyzed only for genotyped LQTS probands who presented with a LQTS-attributable clinical event and were receiving -blocker therapy. The study cohort comprised 28 such patients: 18 KCNQ1/KVLQT1(LQT1), 7 KCNH2/HERG (LQT2), and 3 SCN5A (LQT3). The prescribed -blocker was atenolol (12), propranolol (10), metoprolol (4), and nadolol (2). -Blocker therapy failure was defined as breakthrough cardiac events including syncope, aborted cardiac arrest (ACA), appropriate implantable cardioverter-defibrillator (ICD) therapy, or sudden death occurring while on -blocker therapy. During a median follow-up of 46 months, 7/28 (25%) LQTS probands experienced a total of 15 breakthrough cardiac events. Their initial presentation was ACA (3), bradycardia during infancy (2), and syncope (2). The underlying genotype was KVLQT1 (6) and HERG (1). Two breakthroughs were attributed to noncompliance. Of the 13 breakthroughs occurring while compliant, 10 occurred with atenolol and 3 with propranolol (p = 0.03). In this study cohort, one-fourth of genotyped LQTS probands failed -blocker therapy. Treatment with atenolol, young age at diagnosis, initial presentation with ACA, KVLQT1 genotype, and noncompliance may be important factors underlying -blocker therapy failures.     

遗传性长QT间期综合征KCNQ1基因的新突变

目的　研究遗传性长QT间期综合征 (longQTsyndrome ,LQTS)的临床特点并筛查KCNQ1基因突变。方法　首先按照国际公认的诊断标准 ,确立先证者 ,进行家系调查 ,共有 6个LQTS家系被纳入研究。另选 50名心电图正常且校正QT间期 (QTc)≤ 0 41s的健康人作为正常基因对照。分析先证者及家系成员的临床和心电图资料 ,采用聚合酶链反应 单链构像多态性 (polymerasechainreaction singlestrandconformationalpolymorphism ,PCR SSCP)方法 ,对KCNQ1基因编码区全部序列进行基因突变筛查。阳性结果行DNA测序以明确具体突变位点 ,并进行对照研究。结果　 6个家系中共有LQTS患儿 13例 ,男 5例 ,女 8例。其中 ,猝死 1例 ( 8% ) ;晕厥发作 10例 ( 77% ) ;无症状 2例 ( 15% ) ,分别在家系调查和基因筛查时被发现。共采集到 11例患儿的心电图 ,QT间期为 ( 0 460± 0 0 58)s ,QTc为 ( 0 516± 0 0 58)s。经基因检测发现KCNQ1基因上 2个新的致病性突变位点 3 56 3 57ΔQQ和 62 6 63 1ΔGSGGPP ,分别来自 2个家系。还发现 1个新的多态性位点P448R。此 3个位点均位于编码蛋白C 末端结构域。结论　该研究发现KCNQ1基因的 2个新缺失突变位点和 1个新的多态性位点 ,系国内外首次报道 ,丰富了LQTS离子通道突变的基因库资料     

QTc interval prolongation in children with Turner syndrome: the results of exercise testing and 24-h ECG

Background  Turner syndrome (TS) is the most common sex chromosome abnormality in females. Recently, a prolongation of the rate-corrected QT (QTc) interval in the electrocardiogram (ECG) of TS patients has been reported. A prolonged QTc interval has been correlated to an increased risk for sudden cardiac death, and medical treatment is warranted in patients with congenital long QT syndrome (LQTS). Additionally, several drugs of common use are contraindicated in LQTS because of their effects on myocardial repolarization. The importance of the QTc prolongation in TS patients is not known at present. Materials and methods  Eighteen TS patients with a prolonged QTc interval (group 1) and 11 TS patients with a normal QTc interval (group 2) (mean age 12.6±3.1 vs. 11.8±2.1 years, respectively) were tested. The QTc interval was calculated during exercise testing and during 24-h ECG recordings. Results  None of the patients experienced adverse cardiac events during the tests. The mean QTc interval decreased from 0.467 to 0.432 s in group 1 and from 0.432 to 0.412 s in group 2. During the 24-h ECG, the maximum QTc interval was significantly prolonged in group 1 (0.51 vs. 0.465 s, p<0.05, respectively). We conclude that exercise testing and 24-h ECG recording provide valuable information about the cardiac risk in the single TS patient with a prolonged QTc interval. This helps in counseling these girls, as clear therapeutic guidelines are currently lacking. All authors state that there is no conflict of interests.     

Hypocalcaemia mimicking long QT syndrome: case report

We describe a teenage girl who presented with syncope on exertion and prolonged QT on electrocardiogram (ECG). She was found to be hypocalcaemic due to hypoparathyroidism. Following oral calcium and vitamin D supplementation, there were no further episodes of syncope with normalization of the QT segment. This case highlights the need to consider all causes of a long QT segment.